title: Immunomodulatory effects of vitamin D in peripheral blood monocyte-derived macrophages from patients with rheumatoid arthritis.
abstract: 1,25-Dihydroxyvitamin D (1,25(OH)2D3), the active form of vitamin D, modulates both innate and adaptive immune responses. Emerging epidemiological data has also demonstrated disease-modifying and immunomodulatory effects of vitamin D in a wide range of human autoimmune diseases, including rheumatoid arthritis (RA). To evaluate in vitro effects of 1,25(OH) 2D3 in primary cultures of peripheral blood monocyte-derived macrophages of RA patients, monocyte/macrophages, isolated from peripheral blood mononuclear cells of RA patients and healthy subjects by exploiting their ability to adhere to plastic, were treated with increasing concentrations of 1,25(OH)2D3 for 48 h. TNF-α, IL-1 α, IL-1β, IL-6 and RANKL production was determined by ELISA and nitric oxide (NO) release using the Griess method. Immunocytochemistry analysis was also performed to evaluate alterations in transmembrane TNF-α expression after 1,25(OH) 2D3 treatment. A significant dose-dependent decrease in TNF-α and RANKL production by cultured RA macrophages after 1,25(OH)2D3 treatment was found, whereas a significant reduction in normal cells was observed only at higher concentrations. IL-1 α, IL-1β and IL-6 levels were reduced by 1,25(OH) 2D3 at higher concentrations in all cell populations. TNF-α immunostaining was less intense in treated cells compared with untreated. 1,25(OH) 2D3 significantly reduced NO levels regardless of the concentration used. Vitamin D downregulated proinflammatory mediators in monocyte-derived macrophages, and RA cells appeared more sensitive than normal cells. These effects further provide a rationale for the therapeutic value of vitamin D supplementation in the treatment for RA.
authors.affiliation: Rheumatology Clinic, Department of Medical and Surgical Sciences, University of Foggia, Ospedale "Col. D'Avanzo", V.le degli Aviatori 1, 71100, Foggia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Neve
authors.forename: Addolorata
authors.initials: A
authors.lastname: Corrado
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Cantatore
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016207:Cytokines / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D014807:Vitamin D; D009569:Nitric Oxide